Overexpression of GRP94 in breast cancer cells resistant to oxidative stress promotes high levels of cancer cell proliferation and migration: implications for tumor recurrence.
; ; Guénin, Samuel et al
in Free Radical Biology & Medicine (2012), 52(6), 993-1002
Targeting the altered redox status of cancer cells is emerging as an interesting approach to potentiate chemotherapy. However, to maximize the effectiveness of this strategy and define the correct ... [more ▼]
Targeting the altered redox status of cancer cells is emerging as an interesting approach to potentiate chemotherapy. However, to maximize the effectiveness of this strategy and define the correct chemotherapeutic associations, it is important to understand the biological consequences of chronically exposing cancer cells to reactive oxygen species (ROS). Using an H(2)O(2)-generating system, we selected a ROS-resistant MCF-7 breast cancer cell line, namely Resox cells. By exploring different survival pathways that are usually induced during oxidative stress, we identified a constitutive overexpression of the endoplasmic reticulum chaperone, GRP94, in these cells, whereas levels of its cytoplasmic homolog HSP90, or GRP78, were not modified. This overexpression was not mediated by constitutive unfolded protein response (UPR) activation. The increase in GRP94 is tightly linked to an increase in cell proliferation and migration capacities, as shown by GRP94-silencing experiments. Interestingly, we also observed that GRP94 silencing inhibits migration and proliferation of the highly aggressive MDA-MB-231 cells. By immunohistochemistry, we showed that GRP94 expression was higher in recurrent human breast cancers than in their paired primary neoplasias. Similar to the situation in the Resox cells, this increase was not associated with an increase in UPR activation in recurrent tumors. In conclusion, this study suggests that GRP94 overexpression may be a hallmark of aggressiveness and recurrence in breast cancers. [less ▲]Detailed reference viewed: 32 (6 ULg)
Expression of the helicase-like transcription factor and its variants during carcinogenesis of the uterine cervix: implications for tumour progression.
; ; et al
in Histopathology (2011), 58(6), 984-8Detailed reference viewed: 13 (3 ULg)
High prevalence of high-risk human papillomavirus in palatine tonsils from healthy children and adults.
; ; et al
in Otolaryngology - Head & Neck Surgery (2011), 145(2), 230-5
OBJECTIVE: The aim of this study was to determine the prevalence of human papillomavirus (HPV) in 80 tumor-free tonsils from healthy children and adults using a sensitive E6/E7 type-specific polymerase ... [more ▼]
OBJECTIVE: The aim of this study was to determine the prevalence of human papillomavirus (HPV) in 80 tumor-free tonsils from healthy children and adults using a sensitive E6/E7 type-specific polymerase chain reaction (PCR). STUDY DESIGN: Cross-sectional study. SETTING: Ear, nose, and throat department, university hospital. SUBJECTS AND METHODS: Paraffin-embedded tissues from tumor-free tonsils (TFTs) were evaluated for HPV DNA using GP5+/6+ consensus PCR and subsequent genotyping using E6/E7 type-specific PCR for HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, and 68. The immunohistochemical expression of p16 and p53 was also assessed. RESULTS: In 80 TFTs, the authors identified 10 (12.5%) that tested positive for the following high-risk HPV types: HPV 16 (8 cases), 18 (1 case), and 31 (1 case). Twelve patients (15%) tested positive for HPV infection using the GP5+/GP6+ consensus primers but were negative using quantitative PCR. These patients were considered infected with low-risk HPV types. Fifty-eight TFTs (72.5%) tested negative for both GP5+/GP6+ and type-specific HPV PCR analysis (HPV negative). Among patients infected with HPV, the authors observed a slight increase in frequency with age. CONCLUSION: In TFTs, oncogenic and nononcogenic HPVs were present at a relatively high frequency in children and adults. The presence of high-risk HPV DNA in young children supports the horizontal transmission hypothesis and argues in favor of HPV vaccination at birth. [less ▲]Detailed reference viewed: 25 (6 ULg)
DNA methylation and cancer diagnosis: new methods and applications.
Dehan, Pierre ; Kustermans, Gaëlle ; Guénin, Samuel et al
in Expert Review of Molecular Diagnostics (2009), 9(7), 651-7
Methylation of cytosines in cytosine-guanine (CpG) dinucleotides is one of the most important epigenetic alterations in animals. The presence of methylcytosine in the promoter of specific genes has ... [more ▼]
Methylation of cytosines in cytosine-guanine (CpG) dinucleotides is one of the most important epigenetic alterations in animals. The presence of methylcytosine in the promoter of specific genes has profound consequences on local chromatin structure and on the regulation of gene expression. Changes in DNA methylation play a central role in carcinogenesis. Hypermethylation and consecutive transcriptional silencing of tumor-suppressor genes has been documented in numerous cancers. The identification of target genes silenced by this modification has a great impact on diagnosis, classification, definition of risk groups and prognosis of cancer patients. Here we outline genome-wide techniques aiming at the identification of relevant methylated promoters. Methods and applications allowing clinicians to monitor the methylation of target genes will be also reviewed. [less ▲]Detailed reference viewed: 123 (19 ULg)